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      SARS-CoV-2 infection protects against rechallenge in rhesus macaques

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      Science (New York, N.y.)

      American Association for the Advancement of Science

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          Abstract

          An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log 10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

              Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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                Author and article information

                Journal
                Science
                Science
                SCIENCE
                Science (New York, N.y.)
                American Association for the Advancement of Science
                0036-8075
                1095-9203
                20 May 2020
                Affiliations
                [1 ]Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
                [2 ]Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
                [3 ]Harvard Medical School, Boston, MA 02115, USA.
                [4 ]Oregon Health & Sciences University, Beaverton, OR 97006, USA.
                [5 ]University of North Carolina, Chapel Hill, NC 27599, USA.
                [6 ]Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
                [7 ]Bioqual, Rockville, MD 20852, USA.
                [8 ]Janssen Vaccines & Prevention BV, Leiden, Netherlands.
                [9 ]Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.
                [10 ]Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: dbarouch@ 123456bidmc.harvard.edu
                Article
                abc4776
                10.1126/science.abc4776
                7243369
                32434946
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

                This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                Funding
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: OD024917, AI129797, AI124377, AI128751, AI126603
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI135098
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI007151
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI146779
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: CA225088
                Funded by: doi http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: INV-006131
                Funded by: doi http://dx.doi.org/10.13039/100005205, Janssen Research and Development;
                Award ID: N/A
                Funded by: doi http://dx.doi.org/10.13039/100005615, Beth Israel Deaconess Medical Center;
                Award ID: N/A
                Funded by: doi http://dx.doi.org/10.13039/100012802, Ragon Institute of MGH, MIT and Harvard;
                Award ID: N/A
                Funded by: Mark and Lisa Schwartz Foundation;
                Award ID: N/A
                Funded by: Massachusetts Consortium on Pathogen Readiness;
                Award ID: N/A
                Funded by: doi http://dx.doi.org/10.13039/100000861, Burroughs Wellcome Fund;
                Award ID: N/A
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: OD011092, OD025002
                Funded by: Emergent Ventures, Mercatus Center;
                Award ID: N/A
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI007387
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